DESCRIPTION: (Applicant's Abstract) The purpose of this investigation is to assess how host genetic factors influence the outcome of viral hepatitis B virus (HBV). Approximately 5% of adults and 90% of neonates born to hepatitis infected mothers develop a persistent infection. Immunosuppressed populations such as neonates, hemodialysis patients, diabetics, HIV coinfected, and Down's syndrome patients are more likely to have persistent infection. This suggests that host factors are critical in determining outcome. Human leukocyte antigen (HLA) molecules present HBV antigens to cytotoxic T cells and natural killer cells raising the hypothesis that HLA molecules could be critical to viral clearance. To test this hypothesis, specimens from a large cohort of injection drug users who have been exposed to HBV will be used. The study population has 351 chronically HBV infected participants and 1872 who have cleared the infection. From these, 175 participant with persistent infection and 350 with cleared infection will have MHC class I and class II typing performed these numbers give this study excellent power. Potential cytokine gene markers will be tested on this hepatitis database. A case-control analysis will be used to compare allele frequencies. The genetic studies will be done in collaboration with experienced genetic investigators at the National Cancer Institute. Success is likely because the study utilizes a large, well-characterized cohort who has DNA available combine with a collaborative effort with experienced molecular geneticists.